Search Results (3,734)

Drug delivery systems (DDSs) have attracted significant attention due to their ability to enhance therapeutic efficacy while minimizing side effects. In this study, vancomycin (VCM)-loaded calcium phosphate-liposome (CaPLip) composite nanoparticles were developed as a pH-responsive drug delivery system. The CaPLip nanoparticles were fabricated by in situ calcium phosphate precipitation on preformed liposomal templates in the presence of VCM, allowing the drug to be incorporated within the calcium phosphate matrix and adsorbed onto the CaP-coated surface (VCM-CaPLip). Structural and morphological characterization using FT-IR, XRD, and TEM confirmed the successful formation of calcium phosphate-coated liposomal nanoparticles with particle sizes ranging from 300 to 700 nm and a negative surface charge. The developed system exhibited an overall drug-loading efficiency of 47.28% and effectively reduced the initial burst release under physiological conditions. Equilibrium adsorption studies performed using preformed CaPLip nanoparticles demonstrated that VCM adsorption was well described by the Langmuir isotherm, indicating a high affinity of VCM for the CaP-coated surface under equilibrium conditions. Drug release studies at pH 4.0, 6.5, and 7.4 revealed pronounced pH-dependent behavior, with sustained release at pH 7.4 and accelerated release under acidic conditions. Changes in electrical conductivity provided supporting evidence for calcium phosphate dissolution accompanying drug release under acidic conditions. Kinetic analysis indicated a transition from predominantly diffusion-controlled release at physiological pH to diffusion-dissolution coupled release under acidic conditions. These findings demonstrate that CaPLip nanoparticles provide an effective pH-responsive antibiotic delivery platform and show potential for controlled drug release in infection-associated mildly acidic microenvironments. Full article

Donor-derived infections (DDIs), particularly fungal DDIs, are uncommon but serious complications of solid organ transplantation. We report a case of a 52-year-old woman who underwent deceased donor kidney transplantation complicated by probable donor-derived Candida albicans candidemia with native aortic valve endocarditis, managed medically with prolonged echinocandin therapy followed by suppressive fluconazole. Approximately 14 months post-transplant, she developed progressive rhino-orbital mucormycosis due to Rhizopus oryzae, requiring extensive surgical debridement and prolonged antifungal therapy. Initial treatment with liposomal amphotericin B was limited by nephrotoxicity, prompting transition to isavuconazole for long-term management. Immunosuppression was discontinued to control infection, resulting in graft failure. This case illustrates the complex interplay between donor-derived infection, antifungal exposure, and immunosuppression in transplant recipients. It highlights the potential contribution of antifungal selective pressure to breakthrough mold infections and underscores the importance of early recognition, aggressive multidisciplinary management, and individualized antifungal strategies in this high-risk population. Full article

Liposomal systems are commonly used in drug delivery due to their low toxicity, biocompatibility and biodegradability. In this review, the influence of physicochemical parameters of liposomes, namely size, surface charge, and lipid composition, on biodistribution, dendritic cell uptake, and the character of the induced immune response is examined. The potential of strategies such as targeting C-type lectin receptors, the combined use of toll-like receptor agonists and tolerogenic molecules, and an approach based on high-affinity antigen binding to liposomes via coiled coil-forming peptides is evaluated. Mechanisms of tolerance induction at the humoral, cytokine, and cellular levels are discussed, including the switch from a Th2 to a regulatory T-cell response and the formation of blocking antibodies. Special attention is paid to safety aspects associated with the use of liposomal systems, specifically avoidance of pseudoallergic reactions linked to the complement system activation and the toxicity of cationic lipids, as well as approaches for minimization of these risks. The main obstacles to clinical application and promising directions of further research necessary for the development of effective and safe liposomal allergy vaccines are outlined. This review summarizes current data on the use of liposomal systems for allergen-specific immunotherapy. Full article

Conventional oral and injectable drug administration still struggles with unstable plasma levels, weak targeting, and considerable systemic toxicity, problems that become especially acute in chronic disease management. Implantable and wearable biomedical devices offer one path around these limits, yet device-only platforms continue to fall short on drug loading, release control, and protection of fragile therapeutics. Integrating nanoparticle-based biomaterials into such devices has therefore moved from a research curiosity to a serious clinical strategy. As a result, understanding the design principles, translational challenges, and clinical potential of these hybrid platforms has become increasingly important. This review provides a comprehensive assessment of four major nanoparticle families—polymeric carriers (PLGA, chitosan, and micelles), lipid-based vehicles (liposomes, SLNs, and NLCs), inorganic systems (gold, mesoporous silica, iron oxide, and calcium phosphate), and hybrid composites—focusing on how their physicochemical properties govern drug encapsulation, release behavior, and tissue compatibility. These classes are then linked to specific implantable formats such as drug-eluting stents, nano-enabled scaffolds, and reservoir depots, and to wearable formats including transdermal patches, microneedle arrays, biosensor-coupled patches, and patient-actuated devices. A dedicated section addresses stimuli-responsive release driven by pH, enzymes, temperature, and electrical or magnetic fields, alongside closed-loop platforms that pair real-time biosensing with on-demand dosing. Surface engineering strategies, ligand targeting, antifouling coatings, antimicrobial layers, and immune-modulating chemistries are also discussed, together with the central translational hurdles: long-term stability, foreign body response, scale-up, sterilization, and regulatory classification of combination products. Finally, the review outlines near-term directions, including AI-driven dosing, 4D bioprinting, biomimetic nanocarriers, gene therapy delivery, and bioresorbable electronics, that together suggest where these hybrid platforms are likely to mature next. Full article

The host cellular mechanisms determining whether Dirofilaria immitis (canine heartworm) larvae establish infection remain poorly understood. The Mongolian gerbil (Meriones unguiculatus), a naturally nonpermissive host, mounts a rapid macrophage-dominated peritoneal cellular response to intraperitoneal (IP) larval challenge. To test whether macrophages mediate larval clearance, peritoneal macrophages were selectively depleted with IP clodronate liposomes (100 µL/10 g body weight; days −4 and −1 relative to infection) before challenge with approximately 40 D. immitis third-stage larvae (L3). A rat anti-mouse anti-F4/80 antibody was validated as a cross-reactive macrophage marker in jird peritoneal exudate cells (PECs) by standard and imaging flow cytometry, and depletion efficacy was confirmed prior to infection. Significantly more L3 were recovered from macrophage-depleted jirds (mean = 17.7%; SEM = 6.0%) than from PBS liposome controls (mean = 3.8%; SEM = 1.9%) at 1-day post-infection (p < 0.03). Cytology and flow cytometry confirmed near-complete macrophage depletion, and a significant compensatory neutrophilia was observed in depleted animals (64.5% ± 5.7% vs. 19.6% ± 5.1% in controls; p < 0.0001). These findings establish peritoneal macrophages as the primary innate cellular mediators of D. immitis L3 clearance in a nonpermissive host, providing a validated in vivo framework for mechanistic dissection of filarial host specificity. Full article

Invasive aspergillosis and mucormycosis are life-threatening fungal infections characterized by high early mortality, substantial toxicity, and intensive healthcare resource utilization. While multiple antifungal therapies are recommended in international guidelines, their comparative clinical and economic value remains uncertain, particularly in resource-limited settings. We developed a hybrid decision tree and Markov model to evaluate antifungal strategies, including liposomal amphotericin B, isavuconazole, voriconazole, posaconazole, and caspofungin, from the perspective of the Colombian healthcare system over a 6-month horizon. Health states included clinical response, treatment failure, toxicity, and death. Outcomes included quality-adjusted life-years (QALYs), costs, incremental cost-effectiveness ratios (ICERs), and net monetary benefit (NMB). Deterministic and probabilistic sensitivity analyses were performed. In invasive aspergillosis, isavuconazole provided a modest incremental benefit over voriconazole (+0.022 QALYs), driven primarily by improved tolerability, at an incremental cost of COP 3.4 million, yielding an ICER of COP 154.5 million/QALY. In mucormycosis, liposomal amphotericin B yielded greater survival benefits (+0.035 QALYs) but at substantially higher costs (ICER: COP 494.3 million/QALY). Across willingness-to-pay thresholds, isavuconazole and voriconazole demonstrated more favorable economic profiles, owing to lower toxicity and reduced hospitalizations. These findings highlight that the clinical–economic value of antifungal therapy is primarily determined by early survival gains, toxicity burden, and front-loaded costs. Strategies minimizing toxicity and hospitalization appear more efficient in constrained health systems, whereas survival-maximizing approaches may be justified in severe disease. This integrated analysis supports context-specific antifungal decision-making in the management of invasive fungal infections. Full article

Gyrovirus homsa1 (GyH1) causes immunosuppression and multi-organ damage in young poultry. The VP1 capsid protein (VP1) is a key target for subunit vaccine development; however, recombinant VP1 alone elicits limited immunogenicity and requires an efficient delivery system. Here, we developed a liposomal formulation associated with the GyH1 VP1 protein (LNP-VP1) and evaluated its immunogenicity and preliminary safety in specific-pathogen-free chickens. The prepared LNP-VP1 had a mean particle size of 230.11 ± 5.95 nm, a polydispersity index of 0.204 ± 0.023, a zeta potential of −36.55 ± 0.99 mV, and an apparent encapsulation efficiency of 84.03% ± 2.10%. In addition, immunization of chicks with LNP-VP1 induced robust antigen-specific IgG responses and significantly enhanced the infiltration of CD4⁺ and CD8⁺ T cells in the spleen. Furthermore, cytokine analysis revealed upregulation of IFN-γ, IL-4, and IL-17 levels following vaccination. Importantly, no vaccine-associated histopathological changes were observed in major immune or metabolic organs after immunization. Overall, LNP-VP1 effectively elicited both humoral and cellular immune responses with a favorable safety profile, indicating its potential as a candidate vaccine against GyH1 and providing experimental evidence supporting lipid nanoparticles as a delivery platform for avian subunit vaccines. Full article

Background and Clinical Significance: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome characterized by uncontrolled activation of macrophages and cytotoxic lymphocytes. Secondary HLH is most commonly associated with infections, malignancies, and autoimmune disorders. Visceral leishmaniasis (VL) is an uncommon infectious trigger of HLH, and the considerable overlap in clinical manifestations frequently delays diagnosis. Early recognition of the infectious trigger is essential, because prompt targeted therapy may prevent the need for prolonged immunosuppressive treatment and substantially improve outcomes. Case Presentation: A 68-year-old livestock farmer from northern Greece presented with a one-month history of persistent fever, fatigue, and night sweats. Laboratory evaluation demonstrated pancytopenia, severe hyperferritinemia, hypertriglyceridemia, and elevated soluble interleukin-2 receptor (sCD25) levels. After extensive, relevant screening for other underlying etiologies, which proved to be negative, bone marrow examination revealed hemophagocytosis, while anti-Leishmania serology and polymerase chain reaction (PCR) analysis of bone marrow aspirate confirmed infection with Leishmania infantum. Treatment with liposomal amphotericin B along with intravenous dexamethasone resulted in rapid clinical and laboratory improvement. Serial ferritin and sCD25 measurements closely paralleled clinical recovery, supporting their potential usefulness as biomarkers of treatment response. The patient remained asymptomatic at one-month follow-up. Conclusions: Secondary HLH associated with VL is rare, but potentially fatal. Clinicians should maintain a high index of suspicion in patients presenting with prolonged fever, splenomegaly, cytopenia, and marked hyperferritinemia, particularly in endemic regions. Early diagnosis and prompt initiation of targeted therapy are associated with favorable outcomes. Full article

Background/Objectives: Q fever, caused by Coxiella burnetii, is a zoonotic disease usually treated with doxycycline, but alternative options are needed when doxycycline is unsuitable. This study evaluated inhaled liposomal ciprofloxacin (Apulmiq^®) as a post-exposure prophylaxis (PEP) compared with oral doxycycline in a common marmoset model. Methods: Marmosets were exposed to aerosolised C. burnetii and treated 24 h later with Apulmiq (0.8 mg/kg inhaled), doxycycline (6 mg/kg oral), or placebo for 7 days. Outcomes included fever, weight loss, bacterial burden, histopathology, liver enzymes, and immune responses. Results: Both treatments delayed fever onset and reduced disease severity versus placebo. Doxycycline prevented fever during treatment and significantly reduced bacterial loads in the lungs and spleen by Day 28. Apulmiq slightly delayed the onset of fever and reduced early bacteraemia but was less effective at bacterial clearance. Immune analyses showed macrophage activation and elevation of IFN-γ during acute infection, and adaptive immune responses by Day 28. Conclusions: Inhaled Apulmiq provided partial prophylactic protection but did not achieve bacterial clearance. Doxycycline reduced bacterial burden but did not completely eliminate disease. Inhaled antibiotics may have potential for use as an alternative approach for PEP treatment, although further optimisation and investigation are needed. Full article

Background: Despite extensive development of liposomal antibiotics, the structural determinants governing their stability, release, and biological activity remain poorly understood. This study investigated how the cholesterol content and drug-to-lipid ratio affect membrane organization and thereby determine the physicochemical and biological properties of linezolid-loaded liposomes. Methods: Nine liposomal formulations, varying in their cholesterol content (10–30 wt%) and drug-to-lipid ratios (1–5%), were prepared by thin-film hydration. Membrane organization was analyzed by ATR-FTIR spectroscopy and principal component analysis. Liposomes were further characterized by particle size, ζ-potential, encapsulation efficiency, storage stability, in vitro release in phosphate buffer with and without bovine serum albumin, antibacterial activity against B. subtilis, and antimycobacterial activity in an ex vivo PBMC-derived Mycobacterium tuberculosis granuloma model. Results: The cholesterol content and drug-to-lipid ratio markedly altered membrane interfacial organization, particularly the hydration of the carbonyl and phosphate regions. These structural changes correlated with differences in storage stability, protein-responsive release, and antibacterial activity. Functional behavior was non-monotonic, as 30-L showed the highest overall storage stability, while the apparent release depended jointly on the cholesterol content, drug loading, and medium. BSA altered the composition-dependent release pattern instead of producing a uniform effect. In the exploratory granuloma model, the formulations 10-S, 10-L, and 30-M reduced M. tuberculosis CFU by >99%, whereas free linezolid produced approximately 60% inhibition. Conclusions: Membrane interfacial organization is a key determinant of the functional performance of liposomal linezolid, establishing a structure–property–function relationship that provides a mechanistic basis for the rational design of liposomal antibiotic delivery systems for tuberculosis therapy. Full article

Background: Photodynamic therapy (PDT) is a cancer treatment that combines a photosensitizer (PS), light, and oxygen to generate reactive oxygen species (ROS), leading to tumor cell death. PDT efficacy depends largely on PS accumulation within tumors, prompting the development of third-generation PSs and nanotechnology-based delivery systems. Among these, BODIPYs (4,4-difluoro-4-bora-3a,4a-diaza-s-indacene) are promising PSs due to their favorable photophysical properties, while liposomes improve drug delivery, cellular uptake, and sustained release profiles. This study describes the synthesis of two novel BODIPY derivatives differing in the position of a methyl ester group on the meso-phenyl ring, their incorporation into liposomes, and evaluation of PDT efficacy. Methods: Cellular uptake of BODIPY-loaded liposomes, intracellular ROS generation, apoptosis, necrosis, and lipid peroxidation were assessed by flow cytometry in colorectal and ovarian cancer cell lines. The antitumor activity of the liposomal formulations was further evaluated in both 2D and 3D models using MTT and clonogenic assays. The involvement of ferroptosis and necroptosis in PDT-induced cell death was also investigated. Results: Liposomal formulations significantly enhanced cellular uptake compared with free compounds. Following light activation, both formulations induced potent antitumor effects through multiple cell death mechanisms, including canonical and non-canonical pathways, and maintained strong efficacy in 3D tumor spheroids. Conclusions: Liposome-encapsulated BODIPYs represent promising PDT agents by improving cellular uptake and eliciting robust antitumor activity through complementary cell death mechanisms. Furthermore, the methyl ester substituent on the meso-phenyl ring provides a versatile platform for future conjugation with targeting ligands, supporting the development of third-generation, tumor-targeted photosensitizers and warranting further preclinical investigation. Full article

Functional nanomaterials, such as functionalized nanoparticles, nanofibers, nanocrystals, MXene and liposomes, have emerged as game-changers in tissue engineering, enabling precise modulation of cellular behaviors and dynamic biomimetic microenvironments. This review comprehensively summarizes and discusses the cutting-edge applications of nanomaterials in tissue regeneration (including bone, skin, neural and cardiac tissue regeneration), with a focus on their unique physicochemical properties (e.g., stimuli-responsiveness, nano-topography) and hybrid system design. Recent breakthroughs include 4D-printed shape-memory nanocomposites for irregular bone defects and “smart” wound dressings integrating antibacterial nanoparticles with real-time biosensing. However, clinical adoption remains constrained by unresolved challenges in biocompatibility, scalability of nanomanufacturing, and regulatory ambiguities. We critically analyze these barriers and propose a translational roadmap leveraging AI-driven material design and multi-omics validation platforms to accelerate commercialization. Full article

Caffeine is a promising active for topical pharmaceutical and cosmetic applications; however, its hydrophilic nature can limit passive transport across the stratum corneum and reduce local retention. Although nanoparticle-loaded dissolving microneedles have been explored, few systems combine a hollow porous carrier, a lipid coating, and a polysaccharide matrix within a single controlled-release platform. This study developed thermosensitive dissolving microneedles (DMNs) incorporating caffeine-loaded liposome-coated hollow mesoporous silica nanoparticles (ULp-Caf@HMSNs). Sodium alginate–κ-carrageenan matrices, with and without stearic acid modification, were evaluated for their effects on thermal behavior, mechanical strength, and caffeine release. HMSNs showed a hollow mesoporous structure and high specific surface area, while FTIR supported successful incorporation of the formulation components. Liposome coating increased particle size while maintaining nanoscale dimensions. Hot-stage microscopy showed temperature-dependent structural changes at approximately 33–35 °C, with lower apparent transition temperatures in stearic acid-containing formulations. All DMNs exhibited compression forces comparable to mechanically competent DMNs, with NaAlg–κ-car systems reaching 14.3–15.1 N per array. Free-caffeine DMNs followed non-Fickian release, whereas ULp-Caf@HMSN-containing formulations followed Higuchi diffusion-controlled release and showed slower caffeine release. Stearic acid did not consistently improve release performance. The novelty of this work lies in integrating a hollow silica reservoir, a liposomal coating, and an alginate–κ-carrageenan microneedle matrix within one platform. Overall, the system provides a basis for further evaluation in controlled topical or transdermal caffeine delivery. Full article

Background/Objectives: Olive leaf polyphenols exhibit strong antioxidant and antidiabetic potential. However, their application in nutraceutical and pharmaceutical products is hindered by limited stability, poor solubility, and susceptibility to gastrointestinal degradation. Liposomes offer a viable strategy to enhance their protection and functional performance. Methods: A formulation-driven strategy was employed to develop a gastro-resistant liposomal system for olive leaf polyphenols. Extraction conditions were optimized using a Box–Behnken response surface design to maximize phenolic recovery while ensuring compatibility with phospholipid-based systems. Antioxidant activity and key secoiridoids were assessed by spectrophotometric assays and LC–MS/MS. The optimized extract was incorporated into uncoated and Eudragit^® L100-coated liposomes, which were physicochemically characterized. Antidiabetic effects were evaluated in intestinal STC-1 cells under glucose-induced hyperglycemic conditions. Results: The optimized extract (OE) exhibited high antioxidant activity (124.56 ± 9.57 mg GAE/g, 151.61 ± 2.77 mg TE/g, and 472.92 ± 26.14 mg TE/g in TPC, DPPH and FRAP assays, respectively). LC-HRMS metabolomic profiling confirmed a balanced phytochemical composition, with oleuropein as the main compound (143.144 ± 4.914 mg/g). The optimized Eudragit^®-coated liposomes were spherical unilamellar vesicles with a mean diameter of 101 ± 6.1 nm, moderate polydispersity (0.46 ± 0.02), and a negative zeta potential (−17 ± 3.5 mV). High entrapment efficiency was achieved, reaching 65 ± 2.1% for oleuropein and 96 ± 0.3% for hydroxytyrosol. The structural integrity of the vesicles was maintained during storage and in the simulated gastrointestinal environment. The nanoformulation reduced intestinal glucose uptake and intracellular reactive oxygen species levels, and restored GLP-1 levels. Conclusions: The combination of optimized extraction and liposome-based formulation enabled the development of stable, delivery-ready olive leaf polyphenols for potential nutraceutical and pharmaceutical applications. Full article

Background: Hepatocellular carcinoma (HCC) is a highly lethal malignancy and remains a major contributor to global cancer mortality. In situ vaccination (ISV) holds great potential for HCC therapy. Still, its efficacy is severely limited by intrinsic antigen scarcity and the tumor-associated macrophage (TAM)-mediated inhibition of dendritic cell (DC) maturation and T cell activation. In particular, the M2 TAM-HCC cell crosstalk may further aggravate ISV suppression. Moreover, as an internal organ tumor, HCC requires systemic administration of ISV agents, which often cause severe off-target toxicity. Methods: To address these challenges, we developed secretory phospholipase A2 (sPLA₂)-responsive liposomes co-loaded with the TLR7/8 agonist R848 and the ICD inducer doxorubicin (DOX) via a sequential remote loading method, termed sP-Lips@DR. Results: Incorporation of cholesterol (CHOL) significantly improved DOX encapsulation, and the sequential loading method enabled efficient co-encapsulation of both R848 and DOX. sP-Lips@DR responds to an sPLA₂-overexpressed, mildly acidic microenvironment in HCC, enabling selective drug release. In addition, sP-Lips@DR exhibited sPLA₂-responsive cytotoxicity toward H22 cells and macrophage phenotypic shift. Furthermore, sP-Lips@DR could disrupt the crosstalk between M2-like macrophages and H22 cells in an sPLA₂-responsive manner. Conclusions: Overall, the preparation and in vitro evaluation of sP-Lips@DR demonstrate their potential to enhance ISV efficacy in HCC, providing a solid foundation for future in vivo investigations. Full article